Comparison of Two Treatment Strategies in Patients With an Acute Coronary Syndrome Without ST Elevation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Two Treatment Strategies in Patients With an Acute Coronary Syndrome Without ST Elevation (NCT00445263), a randomized phase 4 study. The primary outcome is Mortality, Myocardial Infarction and Revascularization in Emergency.

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, parallel-group trial with no masking. It records an enrollment of 170 and lists Hospital Avicenne as the sponsor. The study began in 2007-03, had a primary completion date of 2010-12, and is marked terminated. The reason for termination is not reported in the registry record.

The two recorded groups were the Early Invasive Strategy and the Delayed Invasive Strategy. The early strategy paired tirofiban with coronarography within 6 hours; the delayed strategy specified coronarography after 6 hours. The registry’s stated objective was to compare an invasive strategy involving early tirofiban and coronarography within 6 hours of randomization with a conservative strategy. The posted arm descriptions, however, identify both groups as invasive strategies, differing in timing. The record does not explain this difference in wording.

The arm counts for the primary outcome are 83 in the early group and 86 in the delayed group. Random allocation helps create a basis for comparing the assigned strategies, but the registry does not report the sequence-generation method, allocation concealment, or whether the analysis followed original assignment regardless of treatment received. Those details are not reported in the registry record.

The listed secondary outcomes include clinical and electrocardiographic evolution during the first 6 hours, angiographic criteria, troponin peak, left ventricular ejection fraction, length of stay, and hemorrhagic complications. The registry does not provide posted analyses for these outcomes. Information about recruitment flow, protocol deviations, and treatment adherence is also not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Mortality, Myocardial Infarction and Revascularization in Emergency, measured over d30.

The primary endpoint is a composite: mortality, myocardial infarction, or revascularization in an emergency, measured by day 30. The registry records the outcome as a number of participants with an event. A composite endpoint combines multiple clinically relevant events into one outcome, allowing the trial’s primary comparison to concern whether a participant experienced any of its components during the stated period.

Each component may differ in frequency and clinical meaning. Because the posted results give a single count for the composite, they do not show how many participants experienced mortality, myocardial infarction, or emergency revascularization separately. The registry also does not define the criteria used to classify myocardial infarction or emergency revascularization, or clarify whether a participant with more than one component is counted once or more than once. Those endpoint details are not reported in the registry record.

The endpoint is used to compare the two assigned strategies over a common follow-up period. Its value depends on consistent definitions and complete ascertainment in both groups. The registry identifies day 30 as the timeframe, but does not report the follow-up procedures, adjudication process, or handling of participants whose endpoint status was unknown.

7. Results Posted in the Registry

• Delayed Invasive Strategy: 24.4% (21/86) versus 2.4% (2/83) on control; risk difference 22.0 percentage points (95% CI 12.3 to 31.7), risk ratio 10.13 (2.45–41.87); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being compared?

The primary outcome is binary at the participant level: a participant either has at least one event in the composite endpoint by day 30 or does not. The registry gives participant counts with events in each group. For a binary outcome, common summaries include the risk difference, risk ratio, and odds ratio. Each describes the contrast in a different way; none changes the underlying event counts.

The risk difference is an absolute measure. It asks how far apart the event probabilities are between groups. A risk difference of zero would correspond to equal probabilities. Its direction depends on the order used to subtract the groups, so an estimate for delayed strategy relative to early strategy must be interpreted in that order. The posted estimate is positive in that direction, matching the greater number of events recorded in the delayed group.

The risk ratio is a relative measure: it compares the event probability in one group with the probability in the other. A value of one represents equal probabilities. The reported risk ratio is 10.13. Its confidence interval extends from 2.453 to 41.87, indicating that the estimated relative contrast is imprecise even though the interval does not include one.

The odds ratio compares odds rather than probabilities. Odds are related to, but are not the same as, probabilities. An odds ratio of one represents equal odds. The reported odds ratio is 13.08, with a confidence interval from 2.959 to 57.86. When outcomes are uncommon, odds ratios and risk ratios may be closer in value, but they remain distinct measures. These relative estimates should not be interpreted as absolute differences in event probability.

What does the p-value describe?

The registry reports an unadjusted p-value of <0.001. In general, a p-value is calculated under a statistical model that assumes no group difference and describes how unusual the observed data, or more extreme data, would be under that model. It is not the chance that the finding is due to chance, and it does not measure the probability that the treatment strategies are equivalent or different. It also does not indicate the size or clinical importance of the contrast.

“Unadjusted” means the posted comparison is not described as accounting for additional participant-level variables. The registry does not report a model specification, covariate adjustment, or a method for accounting for the trial design beyond the stated randomized allocation. The displayed p-value and effect estimates are therefore best understood as unadjusted comparisons based on the posted summary counts.

Why do event counts matter for precision?

Statistical estimates based on event counts are affected by how many events occur, not only by the total number of participants. With few events, moving a small number of participants between the event and no-event categories can substantially change an estimated relative effect. This is one reason confidence intervals around relative estimates can be wide. The early group has 2 recorded events, compared with 21 in the delayed group; the estimates should be considered in light of these counts.

The registry reports a risk-difference confidence interval as well as intervals for the relative estimates. A confidence interval expresses the uncertainty in an estimate under the method used to calculate it. In general, a wider interval means less precision, while a narrower interval means greater precision. Intervals do not account automatically for every limitation, including possible missing outcomes, outcome misclassification, or unreported analysis choices.

What cannot be inferred from the analysis record?

The registry record does not report the statistical test used for the primary comparison, the confidence-interval method, or whether the analysis was prespecified. It does not report an intention-to-treat or per-protocol analysis population, an approach to missing data, or any adjustment for multiple comparisons. These omissions limit how fully the posted estimates can be evaluated. They do not change the counts and estimates that are recorded, but they leave uncertainty about the analysis procedures behind them.

The listed secondary outcomes concern several different types of measurements, including clinical events, angiographic findings, laboratory measurements, and length of stay. Their appropriate statistical summaries may differ by outcome type. The registry does not post separate analyses for these secondary outcomes, so no conclusions about their results can be drawn from the listed outcome descriptions alone.

10. Confidence Intervals and Precision

The point estimates describe the observed contrast, while confidence intervals communicate uncertainty around those estimates under the statistical method used. For this trial, the reported risk-difference interval is entirely above zero. The registry’s relative-effect intervals are also entirely above the value representing no relative difference. This indicates that the reported intervals do not include their respective null values, but it does not remove uncertainty about the magnitude of the contrast.

The relative intervals are broad: the risk ratio is 10.13, with an interval from 2.453 to 41.87, and the odds ratio is 13.08, with an interval from 2.959 to 57.86. Such breadth means the data are compatible with a wide range of relative effect sizes under the reported analysis. The event counts—2 in the early group and 21 in the delayed group—are important context for that imprecision.

Confidence intervals are not guarantees that the true effect lies within the reported bounds. Their interpretation depends on the model and calculation method, which are not reported in the registry record. They also do not address potential biases from incomplete follow-up, outcome classification, or departures from the intended strategy. The registry does not report enough detail to assess those issues.

The posted intervals quantify statistical uncertainty for the comparison as recorded. They should be considered alongside the trial’s terminated status, the lack of reported component-specific results, and the unreported details of the analysis population and missing-data handling. Precision in an estimate is only one part of evaluating the evidence.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. The registry’s original sample-size justification and design assumptions are not reported in the registry record. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers planning for 100%, 75%, or 50% of the observed effect.

The figures are participants per arm, not total participants and not total events. For planning for 100% of the observed effect, the illustration gives 37 participants per arm for 80% power and 49 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 54 participants per arm for 80% power and 72 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 94 participants per arm for 80% power and 125 participants per arm for 90% power.

In general, power is the probability that a planned analysis will detect an effect of a specified size if that effect is present, under the assumptions of the calculation. The 80% and 90% columns show the illustrative number of participants per arm associated with those target probabilities. A higher target power requires more participants under the same planning assumptions. Likewise, smaller effects need more participants to detect than larger effects.

These calculations use the observed effect as their starting point, which can be unstable when event counts are limited. They are planning illustrations, not observed power. They do not show how the trial was originally planned or whether the trial achieved a particular power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.024; treatment proportion p₁ = 0.244; average p̄ = 0.134.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4820 = 0.9446.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4562 = 0.3839.
4. n = (0.9446 + 0.3839)² / (0.2201)² = 36.4, rounded up to 37 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0240963855421687                          # control proportion
p1 <- 0.244186046511628                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(445263)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 37 (80% power), 49 (90% power)
 75% of observed effect: n per arm = 54 (80% power), 72 (90% power)
 50% of observed effect: n per arm = 94 (80% power), 125 (90% power)
power.prop.test: 36.4 
Simulated power at n = 37 per arm: 0.884 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The primary endpoint combines mortality, myocardial infarction, and emergency revascularization. The registry posts a single comparison for this composite, without separate component counts or estimates. It is therefore not possible to determine from the posted results which component contributed most to the composite contrast, or whether the components showed similar patterns.

Three secondary outcomes are listed, covering clinical and electrocardiographic evolution, angiographic criteria, troponin peak, ventricular ejection fraction, length of stay, and hemorrhagic complications. The registry reports no separate analyses for these outcomes. Whether these outcomes were analyzed, and what their results were, is not reported in the registry record.

When a study assesses multiple outcomes or comparisons, the chance of at least one apparently notable result can increase. Statistical approaches can account for multiple testing, but the registry does not report whether any multiplicity adjustment was planned or used. It also does not report whether the primary endpoint was designated before data analysis or whether there were additional planned analyses.

The registry provides group counts for the primary outcome, but does not state how participants with missing endpoint data were handled. The extent of missing follow-up and the reasons for any missingness are not reported in the registry record. Nor does the record identify the analysis population—for example, whether participants were analyzed according to their randomized group regardless of treatment received, or whether another population was used.

Other analysis details are also not reported, including the statistical test or model, any covariate adjustment, interim analyses, and methods for addressing protocol deviations. These gaps do not negate the posted counts, but they constrain independent assessment of the analysis and the interpretation of the reported p-value and confidence intervals.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: major bleeding (2.4%).

The registry lists serious adverse events for both strategy groups. In the Early Invasive Strategy group, 2 of 83 participants are recorded as having a serious adverse event; in the Delayed Invasive Strategy group, 1 of 86 is recorded. The listed number of participants with other, non-serious adverse events is 0 in each group.

Major bleeding is listed among the serious adverse event terms at 2.4%. The record does not make clear in this summary how that term maps to the group-specific serious-event counts, so it should not be assigned to a particular arm based on the posted figures alone. The registry does not report a death count in the adverse-event summary.

These figures describe the adverse events recorded in the registry; they do not establish that all events were captured or that event rates were compared using a formal statistical analysis. The record does not provide definitions, severity grading details, follow-up duration for adverse-event collection, or a group comparison for safety. The small counts also mean that the posted figures offer limited precision for comparing uncommon events.

15. What the Result Does, and Does Not, Mean

The registry’s posted primary outcome counts are lower in the early strategy group than in the delayed strategy group: 2 participants with the composite event among 83 in the early group, and 21 among 86 in the delayed group. The unadjusted comparison is reported with p < 0.001. The risk ratio and odds ratio estimates are both above one when expressed for delayed relative to early strategy, and their reported confidence intervals are wide.

These results describe the recorded comparison in this randomized trial. They do not establish why the groups differed, identify the contribution of each component of the composite, or show whether the contrast was consistent across participant subgroups. The registry does not report component-specific results, adjusted analyses, or the details needed to assess missing outcome data and the analysis population.

The comparison is between strategies that differ in timing as described in the arm records. It is not a direct estimate of the effect of tirofiban alone, because the early strategy also included earlier coronarography and the delayed strategy description specifies a different timing for coronarography. The registry does not give enough detail to separate the effects of the individual elements of care.

A statistically notable result is not by itself a measure of clinical importance or certainty about the size of an effect. The event counts are limited, and the relative-effect intervals span a broad range. The terminated status is recorded, but the reason for termination is not. These considerations make the registry result a specific, qualified account of the posted data rather than a complete assessment of the strategies in all settings.

16. Why This Trial Matters Statistically

This trial is statistically instructive because it contrasts two strategies using a binary composite endpoint and posts both absolute and relative effect measures. The counts of participants with events are essential context for interpreting the estimates. A large relative contrast can coexist with substantial uncertainty when the number of events is limited, especially in one group.

The confidence intervals show why a single point estimate should not be treated as the complete result. The relative estimates are far from the value representing no difference, but their intervals are wide. Statistical evidence against a no-difference model and precision about the magnitude are related but distinct questions. The unadjusted p-value addresses the former under its model; the intervals give a sense of the latter.

The composite endpoint also illustrates an interpretive trade-off. Combining events creates one primary comparison, but a single composite count cannot show whether its components moved together or whether one component largely drove the result. Component-specific counts and definitions would be needed to answer those questions; they are not reported in the registry record.

Finally, the record demonstrates why trial design and analysis details matter when reading results. Randomization and parallel groups are stated, but important information about allocation procedures, missing data, analysis populations, and multiplicity is not reported. The posted estimates remain informative as recorded observations, while these missing details constrain how completely the statistical evidence can be evaluated.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The record describes a randomized, unmasked, parallel-group study, but does not report the randomization procedure, allocation concealment, or the criteria used to determine eligibility. Participant characteristics and the balance of baseline risk factors between groups are also not reported. These omissions limit assessment of how the enrolled population relates to the intended high-risk population described in the rationale.

The primary outcome is a composite, but the registry does not give separate event counts for mortality, myocardial infarction, and emergency revascularization. Definitions and adjudication procedures for these components are not reported. The record also does not explain whether multiple components in one participant were handled as one participant with an event or counted in another way.

The registry marks the trial terminated without stating the reason. It does not report whether recruitment or follow-up ended as planned, whether any interim analyses occurred, or whether outcome ascertainment was complete. The original sample-size calculation is not reported. The planning illustration based on the observed effect cannot substitute for that missing design information.

For the primary analysis, details about missing data, analysis population, protocol deviations, and statistical methods are not reported. No separate analyses are posted for the listed secondary outcomes. The adverse-event summary also lacks definitions and a formal comparison between groups. These limitations are specific to the information available in the registry record and should be kept in view when interpreting the posted results.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparison of Two Treatment Strategies in Patients With an Acute Coronary Syndrome Without ST Elevation — NCT00445263.
• Registry record last updated 2015-02-27; status last verified 2015-02.
• Results first posted 2015-02-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

NCT00445263 is a Phase 4 randomized, unmasked, parallel-group trial sponsored by Hospital Avicenne. It enrolled 170 participants and is marked terminated. The study began in 2007-03, with primary completion recorded as 2010-12; the reason for termination is not reported in the registry record.

The trial compared an Early Invasive Strategy, described as tirofiban and coronarography within 6 hours, with a Delayed Invasive Strategy, described as coronarography after 6 hours. The primary outcome was mortality, myocardial infarction, or revascularization in an emergency by day 30. The posted event counts are 2 of 83 in the early group and 21 of 86 in the delayed group. The record reports an unadjusted p-value of <0.001 and imprecise relative-effect estimates. Important details about the analysis population, missing data, endpoint definitions, and reason for termination are not reported in the registry record.